OBJECTIVE To determine the effect of dietary restriction on insulin and glucose metabolism in aging macaques with the use of frequently sampled intravenous glucose tolerance tests (FSIGT). Secondly, to perform a small pilot study on the feasibility of conducting radiolabeled euglycemic hyperinsulinemic clamp procedures in dietary restricted and ad libitum-fed aging monkeys. RESULTS Sixty-eight male and female rhesus macaques in three experimental groups were studied as part of an ongoing multidimensional study of the effects of aging and dietary restriction. One half of the animals in each group, with adequate supplemental micronutrients in their diets, have been energy restricted by 20-30%. Restricted (R) compared to ad libitum-fed control (C) monkeys in group 1 studied since 1989 exhibited lower fasting glucose and insulin levels, lower insulin responses, and higher insulin sensitivity indices as determined from minimal model analysis of the semi-annual FSIGT data. Similar results are seen between R and C monkeys in the younger group 2 males and group 3 females studied since 1994. A small pilot study was also conducted with a separate group of eight rhesus macaques using a radio-labeled euglycemic hyperinsulinemic clamp procedure to determine steady state hepatic glucose production, and hepatic and peripheral insulin sensitivity FUTURE DIRECTIONS We intend to continue to perform FSIGT procedures on an annual basis in these three groups. We will also expand the FSIGT protocol to include the use of a stable-labeled glucose isotope, which, while not substantially altering the current protocol, will enable us to model insulin and C-peptide data, and to determine hepatic glucose production. KEY WORDS dietary restriction; aging; glucose metabolism; insulin sensitivity FUNDING NIH P01 AG11915 PUBLICATIONS Gresl, T., Roecker, E., Havighurst, T., Baum, S., and Kemnitz, J. Chronic dietary restriction protects against insulin resistance and type 2 diabetes in adult rhesus monkeys. Diabetes 47(Suppl. 1) A310, 1998. Gresl, T., Cartee, G., Gazdag, A., Roecker, E., Colman, R., Baum, S., Mason, L., and Kemnitz, J. Dietary restriction protects against the development of type 2 diabetes in rhesus monkeys. FASEB Journal 12(4) A254 , 1998.